Various hormones secreted by brain hypothalami and hypophyses are well known. Examples thereof include thyrotropin releasing hormone, luteinizing hormone releasing hormone, somatostatin, adrenocorticotropic hormone(ACTH), growth hormone(GH) and prolactin. The action of these hormones has been well studied. A novel peptide consisting of 38 amino acid residues which has the adenylate cyclase activity was discovered in a different hormone derived from sheep hypophyses. The structure thereof was determined and the peptide was named "PACAP38" (EPA 0 404 652).
The present inventors filed a patent application (Japanese Patent Application No. 1-155791/1990) on cDNA of sheep PACAP38. Further, cDNA of human PACAP38 was cloned from the cDNA library of testes and the amino acid sequence thereof was also determined (Japanese Patent Application No. 1-259924/1990).
The amino acid sequence corresponding to human PACAP38 is the same as that of sheep PACAP38, although there is substitution of some amino acids in the precursors thereof.
In general, when an amino acid sequence such as a bioactive peptide is determined and cDNA is cloned, its expression mechanism can be studied to determine the physical conditions under which transcription and translation of the gene take place. Understanding the expression mechanism aids in the development of drugs for inducing the expression of the gene. PACAP38, a peptide consisting of 38 amino acid residues which enhances adenylate cyclase activity, is one such peptide whose expression mechanism was unknown in the prior art.
Promoter regions, typically located upstream from genes, are activated by factors which result in the synthesis of mRNA coding for the protein.
Some factors which activate promoter regions have been reported. However, most of them are specific to the cells which specifically express the protein.
Human PACAP is a protein secreted by nerve cells and is specifically produced in the hypothalamas. Accordingly, a promoter of human PACAP can possibly produce substances specific to nerve cells.